Psych/Neuro Exam 3 SG Qs (Dr. G)

True or False: 18-20% in the U.S. population has anxiety disorders

True

What Medications can cause anxiety? Withdrawl from which medications can cause anxiety?

Stimulants, Corticosteroids, thyroid meds, some SSRIs and SNRIs (initial), and asthma meds.

Withdrawl from sedatives like benzos

Symptoms of GAD

Excessive worry, restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbances

What is the treatment choice for mild GAD (7-10)?

Psychotherapy, support system, and trying to reduce causes/triggers

Which endocrine condition can cause anxiety? Low vitamin D levels can increase the risk of what psychiatric disorders?

Hyperthyroidism

Depression & Anxiety

What are the 4 classes of medications usually used to treat GAD?

SSRIs, SNRIs, Benzos, Buspirone

What are the pharmacological properties and withdrawal symptoms of benzodiazepines?

AIMS; anxiety, insomnia, muscle tremors, seizures

Withdrawal symptoms are more severe with the short-acting or the long-acting BZDs? Explain.

More severe with short acting because it can get out of body a lot quicker; making the levels drop drastically, leading to withdrawl

How long does it usually take to complete proper tapering of long-term use of BZDs?

Weeks to months

Which benzodiazepine commonly prescribed for anxiety has a relatively short duration of action?

Xanax

Which BZD is considered a considered a long-acting BZD (average half-life of 20-40 hours) without the long-acting active metabolite with half-life of 20-100 hours)?

Clonazepam

What are the potential issues with long-term use of BZDs for the treatment of anxiety disorders?

Tolerance & dependence

Which BZDs can you recommend for patients with compromised hepatic function?

LOT; lorazepam (ativan), oxazepam (serax), temazepam(restoril)

Which BZD is better for IM injections and why?

Lorazepam; better absorption, less painful

What drinks should be avoided with BZDs? Why?

Grapefruit juice and alcohol; grapefruit juice is a CYP3A4 inhibitor

Why are Valium (diazepam) and Xanax (alprazolam) most likely to be abused? Which BZD is least likely to be abused? Why?

They are highly lipid soluble and cross the BBB quickly, oxazepam is the most hydrophilic with less potential for a high

What is flumazenil (Romazicon) used for? Should this be recommended for multiple meds (including BZDs) overdoses?

It is used for the reversal of BZD inducted sedation, do not give to patients with polysubstance overdose

Your patient complains of withdraw symptoms on a stable dose of alprazolam (Xanax) when carbamazepine was added to her medication regimen. Explain why.

Carbamazepine is an inducer and will enhance the Xanax metabolism, causing withdrawl symptoms

What is the precaution with the initial dose of SSRIs for the treatment of panic disorder?  Why?

It must be ½ of starting dose for depression because they can feel like they are causing anxiety, go low and slow

Explain why bupropion (Wellbutrin) is usually not used as treatment for anxiety disorders?

It doesnt have a serotonergic component to it, so it wont treat the anxiety as well

Buspar (buspirone) is only approved for which type of anxiety disorder? What is the issue with Buspar 10 mg po TID PRN anxiety and insomnia?

GAD

PRN is the problem, it has to be taken daily for a period of time, it is not a PRN drug, patients might even experience insomnia from it

Vistaril (hydroxyzine pamoate) 25-50 mg po Q4-6 hours PRN anxiety. What is the proposed MOA for the anxiolytic effects? What are the common side effects?

Antihistamine used for rash

Anticholinergic effects → dry mouth, constipation, urinary retention

What is the anxiety disorder that is often seen in the emergency department as a possible heart attack (myocardial infarction)? What are the symptoms that are similar to MI symptoms?

Panic disorder

Palpitations, shortness of breath, chest pain, etc

What is the issue with using BZDs long-term for treatment of anxiety disorders?

Could lead to tolerance and dependence, possible abuse if it runs in the family

What is the usual medication class recommendation for long-term treatment for panic disorder?

SSRIs

What is the indication for Anafranil (clomipramine)?

OCD

Luvox (fluvoxamine) is FDA-approved only for which anxiety disorder?

OCD

What is the best long-term treatment for PTSD? Why is this type of treatment difficult for patients during the first few sessions?

Psychotherapy/ group therapy

trying to talk and cope with trauma can be difficult

What is the off-labeled medication for PTSD nightmares and flashbacks?

Prazosin

What is the most common phobia? How does propranolol help with this phobia for some people?

Public speaking

Can decrease physiological manifestations if taken 1 hr before

True or False: Bupropion (Wellbutrin) is commonly used for anxiety disorders

False

What is the FDA warning for gabapentin misuse and abuse?

Serious breathing difficulties may occur especially when used with opioids

Explain why patients with alcohol use disorder can tolerate high doses of BZDs. What is “cross tolerance” with alcohol and benzodiazepines?

They act on the same receptor and same mechanism, meaning with high tolerance of one, means high tolerance of another

Which benzodiazepines do not need “Do not drink grapefruit juice” labels. Explain

Non-CYP3A4 and LOT: lorazepam, oxazepam, temazepam

Explain why SSRIs and SNRIs should be started at lower doses for anxiety disorders

It must be ½ of usual starting dose for depression because they can feel like they are causing anxiety. Go low and slow

True or False: There is an equal number of women as men suffering from schizophrenia, but the onset of symptoms is later in women (late 20s) than in men (teens to early 20s).

True???? TBD

For the diagnostic criteria for schizophrenia, patients have to have the symptoms for how many months?

6 months with at least one month of active symptoms

Which neurotransmitters is usually associated with drug-induced psychosis in the mesolimbic area of the brain?

Dopamine (excessive)

What is the mechanism of the older typical antipsychotic agents which helps with positive symptoms, but can worsen negative symptoms?

D2 blockers help with positive symptoms

D2 blockade in mesocortical region of the brain will have negative symptoms

What is the mechanism of action of the atypical antipsychotics?

5-HT2A antagonist

D2 antagonist (less effective for positive symptoms)

Name the 4 dopamine pathways and D2 blocking effects in these areas of the brain.

Nigrostriatal, mesolimbic, mesocortical, and tuberoinfundibular

When 5HT2A receptors are blocked, what happens to dopamine activities? How does this mechanism help with minimizing negative/cognitive symptoms, EPSE, and hyperprolactinemia?

5HT2A blockade increases dopamine in the mesocortical, nigrostriatal, and tuberoinfundibular regions of the brain, reducing EPSE, negative sx, and hyperprolactinemia

Which of 2 atypical antipsychotics have the most EPSE and hyperprolactinemia?

Risperidone and paliperidone

Which 3 atypical antipsychotics have the highest risk for metabolic syndrome?

Clozapine (Clozaril), Olanzapine (Zyprexa), and Quetiapine (Seroquel)

Name the 2 typical and 4 atypical antipsychotic agents with a long-acting injection formulation (OPRAH)

Atypical: Paliperidone, Risperidone, Olanzapine, and Aripiprazole

Typical: Haloperidone and Fluphenazine

A 12-year-old male is in the ED with painful muscle neck spasms. He was given a few days of promethazine for N/V. Explain why antiemetic agents can cause EPSE?

D2 blockers can cause EPSE

What is the most dangerous dystonic reaction with the long-term use of antipsychotic agents? What would you recommend for immediate treatment?

Laryngospasms- IV benztropine 2mg or Diphenhydramine 50 mg

IV is better than IM/PO because of immediate onset

What is AP-induced akathisia and the treatment of choice?

feeling of inner restlessness and compulsion to be in constant motion

Propranolol 30-60 mg/day (max 120 mg)

What are the symptoms of AP-induced Pseudoparkinson’s? What is the treatment of choice for patients with Parkinson’s disease?

akinesia, mask-like face, resting tremor, stooped posture, drooling, or rigidity

Nuplazid (pimayanserine)

What are extrapyramidal side effects (EPS)? What is tardive dyskinesia (TD)? What is the proposed mechanism that causes TD?

repetitive involuntary movements

caused by long term use of D2

What are the FDA-approved treatments for TD after discontinuing the offending drug?

Ingrezza (Valbenazine) or Austedo (Deutetrabenazine)

DDI with CYP2D6 and CYP3A4

Your patient on an antipsychotic was found to have body rigidity, altered consciousness, unstable BP and HR, fever, and diaphoresis. What should you recommend for neuroleptic malignant syndrome (NMS)?

Benzos, bromocriptine

Which 2 atypical antipsychotics’ PK is affected by cigarette or marijuana smoking? Explain DDI MOA.

Clozapine & Olanzapine

Smoking → CYP1A2 induction

What happens when patients are stabilized on these antipsychotics in a non-smoking hospital and upon hospital discharge, they resume their smoking habit?

Doses need to be increased to maintain therapeutic levels

smoking induces 1A2 metabolism of clozapine & olanzapine

What is the boxed warning for clozapine?

agranulocytosis, orthostatic hypotension, seizures, myocarditis & cardiomyopathy,and increased risk for elderly

What is agranulocytosis? How frequent is ANC monitoring (CBC w/diff)?

drug induced blood disorder w/ severe reduction in the number of WBC

Frequency: 1-6 months every week, 6-12 months every other week, post 12 every month

1.     What antibiotics should be used with caution for patients on clozapine/olanzapine? Why?

Fluroquinolone antibiotics

Due to 1A2 inhibition

Which 2 atypical antipsychotics should be taken with food for increased bioavailability?

ziprasidone (geodone) and lurasidone (latuda)

True or false: Cobenfy should be taken with food.

False

What is wrong with the following order for Saphris 5 mg PO BID? What patient education is important for the administration of this medication?

Saphris is SL not PO

place under tongue and let dissolve, avoid eating/drinking 10 mins before and after admin

Your patient complains of severe dizziness when he started on Seroquel 100 mg BID. Why?

initial dose should not be more than 100 mg per day due to orthostasis

Seroquel is a potent alpha-1 blocker so it must be titrated

What is the boxed warning for antipsychotic use in the elderly with dementia-related psychosis?

elderly patients with dementia related psychosis treated with antipsychotic drugs have a 1.6-1.7x greater risk of death

What is the FDA-approved treatment for Parkinson’s psychosis?

Pimavanserin (Nuplazid)

Off label: clozapine and quetiapine

What are the advantages and disadvantages of the atypical antipsychotics vs. the older typical antipsychotics?

typical antipsychotics are more effective for psychosis but have more EPS

atypical have fewer EPS but some have high risk for metabolic syndrome (Clozapine, olanzapine, and quetiapine)

Which atypical antipsychotic with long-acting injectable formulation has the post- injection delirium/sedation syndrome?

Patients have to be observed for 3 hours after each injection

Zyprexa Relprevy (Olanzapine) rare

A 30-year-old male patient on risperidone w/ high prolactin complains of developing “moobs.” What is the medical term for this side effect from hyperprolactinemia?

Gynecomastia

What is the most common EPS (dystonia, akathisia, Pseudo-Parkinson’s) seen with Aripiprazole (Abilify)? What is the treatment of choice for this EPS?

Akathisia

beta blockers → propanolol

What is the interaction between valproic acid & paliperidone? Mechanism of Interaction?

Valproic Acid inhibits metabolism of drugs that are metabolized by hepatic phase 2 metabolism

VPA inhibition of glucuronidation can increase paliperidone concentration by 50%

What antipsychotics are FDA-approved for bipolar depression? Why is monotherapy with antidepressants not recommended for bipolar depression?

quetiapine, olanzapine, lurasidone, cariprazine, lumateperone

monotherapy w/ antidepressants for bipolar disorder may induce hypomania/mania

Which antipsychotic is used at low doses for off-labeled treatment of insomnia?

Quetiapine (Seroquel) 100 mg po QHS PRN insomnia

Discuss the best and worst choices for patients with sedation, EPS, and weight gain

Worst: clozapine, quetapine and olanzapine, 1st gen

Best: Risperidone, paliperidone, aripiprazole

Clozapine is reserved for treatment refractory schizophrenia due to lower efficacy in treating symptoms of schizophrenia (T/F).

False

What is the role of samidorphan in the combination medication Lybalvi (olanzapine/samidorphan)?

MU antagonist included to reduce weigh gain associated with olanzapine

Which class of medications should not be used concurrently with Lybalvi? Why?

Opioids

can cause withdrawl effects

What are the symptoms of bipolar mania?

abnormal elevated mood lasting at least one week, distractibillity, impulsivity, grandiosity, flight of ideas, decreased sleep, talkativeness

What is the difference between bipolar 1 and bipolar 2 disorders? Why is bipolar 2 disorder often misdiagnosed as major depression? What is the issue with dx of MDD instead of BP2 disorders in terms of treatments?

Bipolar 1: Mania and depression
Bipolar 2: Hypomania (mild mania) and depression, often Dx as MDD bc they have same Sx
Bipolar treated with AD can cause mania due to increase in DA, 5HT, NE, etc

T/F There are more women than men with bipolar disorders.

False

What is the average age of onset of bipolar disorders?

20s

What is the danger of a misdiagnosis of ADHD instead of bipolar disorder?

ADHD is treated w/ stimulants and stimulants can worsen bipolar mania

What are the similarities with some symptoms between bipolar mania and ADHD?

DIGFAST

mood instability in bipolar mania

inattention in ADHD

What are the symptoms experienced during bipolar depression and major depression because they're the same (D/A+SIGECAPS)?

D/A: Depressed mood or Anhedonia
S: Sleep disturbance
I: Interest
G: Guilt
E: Energy
C: Concentration
A: Appetite
P: Psychomotor agitation/retardation
S: Suicidal thoughts

What is the main difference with treatment of MDD and bipolar depression?

Depression: ADs

Bipolar: 2nd gen antipsychotics and mood stabilizers

What is your recommendation for a bipolar patient with manic symptoms on Prozac 20 mg QAM?

Discontinue

What baseline labs are needed for lithium therapy? Why?

BUN and SCr (Renal function)
Urine Specific gravity (affect kidney's ability to concentrate urine)
Thyroid function test (hyperthyroidism=mania)
CBC differential (leukocytosis, hyponatremia=low elim of lith)
Optional: EKG (bradycardia) and pregnancy (lithium affects heart dev)

What is the usual therapeutic lithium level range?

0.6-1.2 mEq/L

How many hours post-dose would you educate your patient on lithium to go get labs for their lithium levels? Why?

Labs 10-12 hours after because drug has narrow therapeutic index
Small fluctuations can cause toxicity
You have to wait that time so you don't get falsely high levels and falsely adjust therapy

What common DDIs can cause higher and possible toxic lithium levels?

DDIs: NSAIDs (inhib metab.) and Thiazide diuretics (inhib metab.)

What are the symptoms of lithium toxicity? What can be recommended for a patient with lithium toxicity?

Common: Confusion, ataxia (poor coordination), slurred speech, lethargy
Hand tremor, vomiting, diarrhea, CNS depression, arrhythmias, seizures, coma
Tx: Hold lithium doses or give 0.9% NaCl IV infusion or hemodialysis

Lithium has a delay in onset of action (2-3 weeks). What medications are usually prescribed for acute mania before lithium's onset of action?

Sedating antipsychotic: Olanzapine/Zyrexa
Benzodiazepine to calm the patient down (do not use long term)

Which atypical antipsychotics are FDA-approved for bipolar depression?

CLOQ
Cariprazine/Vraylar
Lurasidone/Latuda
Olanzapine/Zyprexa, Olanzapine+Fluoxetine/Symbyax
Quetiapine/Seroquel

What indications is Caplyta/Lumaterperone approved for? What are 2 common ADRs?

Bipolar (1 or 2) depression
Common ADR: Sedation and weight gain

What CrCl should patients should not be on lithium therapy?

CrCl: <30 ml/min

Explain the effects of a 2-gm sodium restriction diet for your patient on lithium. Explain the mechanism of action for this effect.

More reabsorption of Na and Li which leads to higher Li concentration which can increase ADRs or toxicity

Which anticonvulsants are prescribed for the treatment of bipolar disorder?

CODL
Carbamazepine
Oxcarbamazepine
Divalproex
Lamotrigine

What is the advantage of Depakote® vs. Depakene®? What is the problem with using antacids with Depakote®?

Depakote: enteric coating and is designed to be released in the small intestine to reduce GI side effects
Depakene: IR
Antacids decrease stomach pH which dissolve the enteric coating in Depakote which leads to more GI side effects

What is the problem with using CBZ or VPA during pregnancy?

Higher risk for ASD (Austism Spectrum Disorder)
VPA: Neural tube defects like spina bifida

You have a patient with a new Rx for carbamazepine (CBZ). She is also on oral contraceptives. What do you need to inform the patient and her provider?

That she isn't pregnant or isn't planning to get pregnant
Carbamazepine is an inducer which can reduce efficacy of contraceptive

Lamotrigine is FDA-approved for the treatment of maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy." Is lamotrigine effective for acute bipolar mania?

Not effective for acute bipolar mania, it's better for bipolar depression

What is an important patient education point for patients starting on lamotrigine? Why?

Monitor for rash because of Steven Johnson Syndrome
If rash occurs, discontinue therapy

What is the dosing precaution with the use of lamotrigine/Lamictal for patients on valproic acid/Depakene or divalproex sodium/Depakote. Why?

Start at half the dose because absorption is limited